The Princess Margaret Phase I Consortium (PMPIC), led by Dr. Lillian Siu, consists of the Princess Margaret Cancer Centre (PM) as its Lead Academic Organization (LAO) and three Affiliated Organizations (AO): Moffitt Cancer Center (MCC), Juravinski Cancer Centre (JCC) and British Columbia Cancer Agency (BCCA). The Specific Aims of PMPIC resonate closely with the goals of the ET-CTN: 1)To conduct innovative, coordinated, efficient, regulatory-compliant and high impact early phase clinical trials in experimental therapeutics, which are designed to address important questions that do not duplicate research supported by the pharmaceutical industry or other sources; 2) To adopt a team science interdisciplinary approach with internal and external collaborations to enhance the optimal evaluation of novel anticancer agents alone or in combination; 3) To accelerate biomarker development and correlative sciences research through comprehensive molecular characterization of tumors obtained from patients enrolled on ET-CTN trials to elucidate mechanism of action, as well as predictors of therapeutic response and/or resistance; and 4) To emphasize training and education to foster career development of junior investigators. PMPIC is committed to actively lead ET-CTN early phase trials as well as to contribute as a meaningful partner to ET-CTN trials led by other Consortia. With a strong Leadership that is supported by the Steering Committee, Translational Research, Clinical Research and Operational Cores, PMPIC embraces a team science approach to conduct the most relevant early phase clinical trials of novel agents alone or in combination. All patients enrolled by the PMPIC will undergo comprehensive molecular characterization using advanced genotyping or targeted sequencing approaches to help identify drivers of drug sensitivity or resistance. This data, along with pharmacological, immune function, and quantitative imaging data, will enable the most optimal biological correlation with clinical outcome. Leveraging resources from other sources including institutional support, the PMP1C will further advances whole exome/whole genome next generation sequencing technologies within the timeframe of this award in the next 5 years.